Key Findings Summary
The patent infringement litigation between Onyx Therapeutics, Inc. (a subsidiary of Amgen Inc.) and Aurobindo Pharma USA, Inc. centers on Aurobindo’s attempt to market a generic version of Onyx’s multiple myeloma drug, Kyprolis® (carfilzomib). Filed in the U.S. District Court for the District of Delaware in 2017, the case alleges that Aurobindo’s Abbreviated New Drug Application (ANDA) No. 210823 infringes patents covering Kyprolis’ compound and formulation. This analysis examines the litigation’s background, legal arguments, and broader implications for pharmaceutical patent disputes under the Hatch-Waxman Act.
Background of the Litigation
Corporate and Product Context
Onyx Therapeutics, Inc., a Delaware corporation and subsidiary of Amgen Inc., holds New Drug Application (NDA) No. 20-2714 for Kyprolis®, a proteasome inhibitor approved in 2012 for relapsed or refractory multiple myeloma[1][2]. The drug’s commercial success—with global sales exceeding $1 billion annually—has made it a frequent target of ANDA filings by generic manufacturers, including Aurobindo Pharma USA, a Delaware-based subsidiary of Indian pharmaceutical giant Aurobindo Pharma Ltd.[1][5].
Aurobindo’s ANDA No. 210823 seeks FDA approval to market a generic carfilzomib product before the expiration of Onyx’s patents listed in the Orange Book for Kyprolis[1][5]. Under the Hatch-Waxman Act, such filings automatically trigger patent infringement claims if the applicant certifies that the patents are invalid or not infringed (a “Paragraph IV certification”)[1][9].
Legal and Procedural History
Initial Complaint and Jurisdictional Basis
Onyx filed its complaint on November 22, 2017, asserting infringement of U.S. Patent Nos. 7,417,042 (‘042 Patent), 8,207,125 (‘125 Patent), and 7,737,112 (‘112 Patent)[1]. These patents cover Kyprolis’ active ingredient (carfilzomib), its synthesis methods, and its lyophilized formulation[2][6]. The District of Delaware exercised jurisdiction based on Aurobindo’s incorporation in Delaware and its prior litigation activities in the district[1][9].
Consolidated Litigation and Settlements
The case was part of a broader consolidated action (Civil Action No. 16-988-GBW) involving multiple defendants, including Cipla Ltd., Apotex Inc., and Fresenius Kabi USA[5][7]. While most defendants settled or entered consent judgments before trial, Aurobindo’s status remains unclear from publicly available documents. However, Aurobindo’s litigation history—such as its 2018 settlement with Ironwood and Allergan over LINZESS® patents—suggests a propensity to resolve disputes through licensing agreements rather than protracted trials[3][7].
Key Legal Issues
Patent Infringement Under 35 U.S.C. § 271(e)
Onyx alleged that Aurobindo’s ANDA submission constituted an act of infringement under 35 U.S.C. § 271(e)(2)(A), which deems ANDA filings seeking approval for a generic drug before patent expiration as statutory infringement[1][6]. The company argued that Aurobindo’s proposed product would infringe claims related to:
- Carfilzomib’s chemical structure (Claims 23–24 of the ‘042 Patent and Claim 1 of the ‘125 Patent)[2][6].
- Lyophilized formulation stability (Claims 31–32 of the ‘112 Patent)[2][6].
Invalidity Defenses and Obviousness Challenges
Aurobindo likely asserted invalidity defenses, including obviousness under 35 U.S.C. § 103, as seen in parallel litigation against Cipla[6][12]. In Onyx v. Cipla, the court rejected obviousness arguments regarding carfilzomib, emphasizing that prior art did not disclose the compound’s specific epoxyketone pharmacophore or its unexpected efficacy in multiple myeloma[6][12]. The court applied a lead compound analysis, requiring defendants to prove that a person of ordinary skill in the art (POSA) would have selected and modified prior art compounds to arrive at carfilzomib—a burden Cipla failed to meet[12].
For formulation patents, Aurobindo might have argued that the lyophilization process was routine optimization. However, in Onyx v. Cipla, the court upheld the ‘112 Patent’s validity, noting that prior art taught away from lyophilizing carfilzomib due to its instability, and the claimed formulation achieved unexpected shelf-life improvements[2][6].
Strategic Implications and Settlement Dynamics
Aurobindo’s Litigation Patterns
Aurobindo’s frequent ANDA challenges—seen in cases involving LINZESS®, Cleviprex®, and Kyprolis®—reflect a business model centered on securing early generic entry through litigation or settlement[3][10]. In the LINZESS® case, Aurobindo accepted a license effective in 2030, avoiding pre-trial risk[3]. Similar behavior in the Kyprolis® litigation could explain the lack of publicly available trial rulings.
Economic Considerations
The District of Delaware’s cost-shifting rulings in Hatch-Waxman cases create financial disincentives for defendants to proceed to trial. For example, in Onyx v. Cipla, the court awarded Onyx $48,146.36 in costs, including deposition and trial transcript fees[5][7]. These dynamics likely pressured Aurobindo to settle rather than risk a costly loss.
Comparative Analysis with Precedent
Obviousness Standards in Compound Patents
The Onyx v. Cipla decision underscores the high bar for proving obviousness of proteasome inhibitors. The court rejected Cipla’s argument that carfilzomib was an obvious modification of prior art compounds (e.g., epoxomicin), noting:
- No motivation to replace epoxomicin’s aldehyde group with an epoxyketone[6][12].
- Unexpected binding affinity and selectivity for the 20S proteasome[2][12].
This precedent heavily favors Onyx’s position against Aurobindo, as the same patents and prior art are at issue.
Formulation Patent Non-Obviousness
Courts have consistently upheld the ‘112 Patent’s formulation claims, emphasizing that lyophilization was not a predictable solution for carfilzomib’s instability. In Onyx v. Cipla, experts testified that POSAs would have pursued liquid formulations instead, given the technical challenges of lyophilizing epoxyketone compounds[2][6].
Conclusion and Industry Impact
Likelihood of Settlement
Given Aurobindo’s settlement history and the strong validity precedents favoring Onyx, the parties likely reached a confidential agreement delaying Aurobindo’s generic launch until after Kyprolis®’s patent expiration (estimated in 2027–2030). Such outcomes align with industry norms, where 79% of Hatch-Waxman cases settle before trial[3][9].
Broader Implications for ANDA Litigation
- Lead Compound Analysis: Courts continue to require defendants to identify a clear lead compound in prior art, complicating obviousness defenses for structurally complex molecules[12].
- Formulation Innovations: Patents covering stability improvements remain robust if supported by unexpected results, even when using conventional techniques like lyophilization[2][10].
- Cost-Shifting Risks: Delaware’s willingness to tax costs against ANDA filers discourages speculative invalidity defenses, reinforcing the economic viability of settlements[5][7].
This case exemplifies the strategic interplay between patent holders and generic manufacturers in balancing litigation risks and market exclusivity periods. For Amgen, successful defense of Kyprolis® patents ensures continued revenue from a critical oncology product; for Aurobindo, settlements provide a pathway to future generic market entry without costly trials.
Key Takeaways
- Onyx’s patents for carfilzomib and its formulation have withstood multiple obviousness challenges, setting a high bar for ANDA filers.
- Aurobindo’s litigation strategy favors settlements over trials, minimizing financial risks.
- Delaware’s cost-shifting rulings incentivize early resolutions in Hatch-Waxman cases.
- Formulation patents leveraging unexpected stability data remain enforceable despite routine manufacturing methods.
FAQs
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Why did Onyx sue Aurobindo?
Onyx alleged Aurobindo’s ANDA for generic Kyprolis® infringed patents covering the drug’s compound and formulation.
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What is the significance of the District of Delaware in this case?
Delaware is a preferred venue for patent cases due to its expertise and defendant-friendly incorporation laws.
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How do Hatch-Waxman settlements affect drug prices?
Settlements often delay generic entry, maintaining higher brand-name drug prices until patent expiry.
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Could Aurobindo win an obviousness defense?
Precedent suggests unlikely success given Onyx’s prior victories against similar arguments.
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What is the status of Aurobindo’s ANDA?
While not publicly disclosed, the ANDA likely remains tentative pending patent expiry or settlement terms.
"The ANDA framework balances innovation and competition, but outcomes often hinge on complex evidentiary standards for patent validity." [1][6]
References
- https://insight.rpxcorp.com/litigation_documents/12757651
- https://www.ded.uscourts.gov/sites/ded/files/opinions/16-988_0.pdf
- https://investor.ironwoodpharma.com/press-releases/press-release-details/2018/Ironwood-and-Allergan-Announce-Settlement-with-Aurobindo-Pharma-Resolving-LINZESS-linaclotide-Patent-Litigation/default.aspx
- https://www.supremecourt.gov/DocketPDF/22/22A272/242488/20221005104421628_Respondents%20Appendix%20A%20PUBLIC%20VERSION%20Novartis%20v%20HEC%2022A272.pdf
- https://www.ded.uscourts.gov/sites/ded/files/opinions/16-988_1.pdf
- https://caselaw.findlaw.com/court/us-dis-crt-d-del/2064246.html
- https://casetext.com/case/onyx-therapeutics-inc-v-cipla-ltd-4
- https://info.vizgen.com/hubfs/Vizgen%20Redacted%20Public%20Second%20Amended%20Complaint_042523.pdf?hsLang=en
- https://insight.rpxcorp.com/litigation_documents/13987617
- https://paragraphfour.com/wp-content/uploads/2019/10/njdc19cv18756Opinion.pdf
- https://www.cadwalader.com/resources/patent-litigation-tracker/patent-specific-hearings
- https://www.jdsupra.com/legalnews/onyx-therapeutics-inc-v-cipla-ltd-75218/
